Likely source for global M. chimaera infection identified by whole genome sequencing

Scientists from a European Consortium reconstructed a global Mycobacterium chimaera outbreak by whole genome sequencing. The report has identified contaminated heater-cooler units as the likely source of Mycobacterium chimaera infection in 21 open-heart surgery patients in Switzerland, Germany, the Netherlands, and the UK, and a further 12 in the USA and Australia, according to a study in The Lancet Infectious Diseases journal. The study was coordinated by DZIF Scientists at Research Center Borstel and by scientists from the University Hospital Zurich, Switzerland.

"The infection with Mycobakterium chimaera likely occured during open-heart surgery, where heater-cooler units were used for regulating the blood temperature", says Prof Stefan Niemann, group leader at the Research Center Borstel and coordinator of the DZIF research area „Tuberculosis". Previous studies have suggested a link to contaminated heater-cooler units used during open-heart surgery, but until now, there has been no firm evidence linking the global outbreak to a source. This evidence should be provided by applying whole genome sequencing. 

The new study analysed the DNA from a total of 250 M. chimaera samples. This included samples from 21 open-heart surgery patients in Switzerland, Germany, the Netherlands, and the UK, as well as samples collected from heater-cooler units, other water-containing medical devices, tap water, and drinking water dispensers in hospitals. In addition, the researchers included samples from patients with M. chimaera from Switzerland, Germany, the Netherlands and the UK who had not undergone open-heart surgery.

M. chimaera belongs to the so called nontuberculous mycobacteria, to be found in natural water reservoirs and normally harmless. An infection of patients with immune deficiencies e.g. can cause lung problems. Studies in 2013 to 2015 also revealed that infection with M. chimaera bacteria during open-heart surgery can cause prosthetic valve endocarditis (infection of the inner lining of the heart) and spread to the rest of the body.

The similarity of samples from almost all patients with M. chimaera infection following open-heart surgery strongly points to a common source of infection. Based on high degrees of similarity between isolates of M. chimaera in these patients' samples, samples from special heater-cooler units and from their production site, the authors say that it is probable that these heater-cooler units represent the common source of infection and that contamination occurred during production.

Professor Stefan Niemann, co-author of the study says: “Molecular epidemiological investigation by applying whole genome sequencing is the most powerful tool for tracing pathogen transmission. Our study closes the missing gap and provides evidence that the international health-care related M. chimaera outbreak can most likely be attributed to a point source.” Professor Dr Hugo Sax, University Hospital Zurich, Switzerland, and co-author of the study, adds: “Local contamination of heater-cooler units with M chimaera also occurred and at least one patient could have been infected through this route. Operating rooms and other hospital settings with patients at increased risk of infection should be devoid of such uncontrolled water sources.”

Infection with M. chimaera bacteria during open-heart surgery is rare during open-heart surgery (UK estimates suggest 1 in 5000 patients ), but potentially fatal. Since 2013, over 100 cases of M. chimaera infection have been reported in the EU, the US, and Australia, and many countries have issued guidance to reduce the risk of infection.

The new study provides crucial hints towards the source of contamination of heater-cooler units and potential ways of infection. Whole genome sequencing is a powerful tool for tracing pathogen transmission and for establishing more effective control mechanisms.

The study was partially funded by the EU Horizon 2020 programme, its FP7 programme, the German Center for Infection Research (DZIF), the Swiss National Science Foundation, the Swiss Federal Office of Public Health, and National Institute of Health Research Oxford Health Protection Research Units on Healthcare Associated Infection and Antimicrobial Resistance.

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